Antioxidants have been studied extensively to identify how they influence human health. They include phytochemicals, vitamins, and other nutrients that protect cells from damage caused by free radicals. They can be found in fruits and vegetables as well as culinary and medicinal herbs.
Oxidative stress is associated with the pathogenesis of a variety of diseases. As a result, antioxidants have been used to combat or minimize the damaging effects of those diseases on the body.
For instance, chlorogenic acid and caffeic acid are two antioxidants implicated in the prevention of type-2 diabetes mellitus (T2DM; Paynter et al., Am J Epidemiol (2006) 164:1075-1084) and in cardiovascular disease (Morton et al., Clin Exp Pharmacol Physiol (2000) 27:152-59). Ingestion of chlorogenic acid improves glucose tolerance in obese Zucker rats resulting in diminished postprandial blood glucose concentrations (Sotillo and Hadley, Nutritional Biochem (2002) 13:717-726) with similar effects indicated in human trials (Johnston et al., Am J Clin Nutr (2003) 78:728). Marketed under the trade name Svetol™, chlorogenic acid has also been approved in Norway and the United Kingdom as a food active ingredient used in coffee, chewing gum, and mints to promote weight reduction.
Ferulic acid, a flavonoid, is another antioxidant having a wide range of therapeutic effects, including anti-inflammatory, anti-atherogenic, anti-diabetic, anti-ageing, neuroprotective, radioprotective and hepatoprotective properties (Srinivasan et al., J Clin Biochem Nutr. (2007) 40: 92-100). Ferulic acid is often added as ingredient of herbal supplements.
Rutin, a citrus flavonoid glycoside found in a variety of fruits and vegetables including asparagus, citrus fruits, and berries, is used in medications for blood vessel protection and as an ingredient in multivitamin preparations and herbal remedies. It has been shown to have anti-inflammatory properties (Selloum et al., Experim Tox Path (2003) 54:313-318), and is a known anti-oxidant.
While plants, vegetables, and fruits are common sources, there are very few that are naturally antioxidant-rich. Thus, a tremendous effort has been deployed in the past several years to find sources of antioxidants that produce a health effect.
One approach to this problem has been to increase antioxidant levels in crops through genetic modification. WO2008/005474 (High level antioxidant-containing foods. Publication Date Jan. 10, 2008 Rommens, C.; PCT/US2007/015437) describes methods of genetically modifying Solanaceous crops, including potato, tobacco, tomato, capsicum, and eggplant by inserting a chlorogenic acid-inducing gene (Cai). Despite the scientific merit, genetically modified (GM) plants pose risks to non-transformed food chain crops and regulatory approval must be obtained before widespread use.
Methods of extracting antioxidants from different plants have also been developed to produce nutraceuticals and food additives with health benefits. As an example, EP1949792 (The healthy and functional foods for the obesity patients using purple-colored potatoes. Publication Date Jul. 11, 2007 Lim, H. K et al.; 07013597.5) describes functional foods and food additives with obesity-suppressing activity that are manufactured using an aqueous extract of the purple potato Solanum tuberosum L. cv. Bora Valley.
JP2007119346 describes conjugates of quinic acid and caffeic acid derived from the leaves and stems of sweet potatoes (Ipomoea spp.) that have anti-diabetic properties. WO2006/014028 (International Application No.: PCT/JP2005/014799. Suzuki, S.; Kitani, S.; Yasutani, I.; Sweet potato stem extract and use thereof Publication Date: Feb. 9, 2006, International Filing Date: Aug. 5, 2005) also describes extracts from the stalk and leaves of sweet potato enriched in polyphenol, and which are useful for preventing and treating obesity. JP2006230225 describes food additives for suppressing increases in blood glucose levels, including triterpene derivatives, hydrolysis-type tannins, ellagic acid or chlorogenic acid, and which are derived from plants of the genus Gymnema, guava leaves, plants of the genus Turminalia, or sugarcane. Compositions comprising caffeine and chlorogenic acid have even been used in cosmetics with slimming properties (FR2883472) (Milesi et al.; FR20050002886 20050323).
Obesity and type 2 diabetes mellitus have become a significant public health issue. It has been suggested that certain plant metabolites can prevent and treat obesity and diabetes via modulation of cellular signaling pathways. Said plant metabolites, ingested as typical dietary components, are considered as relatively safer alternatives to drug-based therapeutics for obesity, insulin resistance and type 2 diabetes mellitus (Liu et al 2010, Biochim. Biophys. Acta 2010, 1799, 854-865; Shehzad et al., 2011, Eur. J. Nutr. 50, 151-161). As the chemopreventive activity of fruits and vegetables are mainly associated with their phenolic compounds, studies determined the bioactivity of specific polyphenolic compounds (Hanhineva et al 2010, Int. J. Mol. Sci. 11, 1365-1402). Polyphenols were suggested to exert their hypoglycemic properties partly by inhibiting digestive enzymes (Bravo, 1998, Nutr. Rev., 56, 317-3330) and lowered the glycemic index inversely correlated with their intake (Thompson et al., 1984, Am. J. Clin. Nutr. 1984, 39, 745-751).
However, the complexity of phytochemical mixtures in fruits and vegetables could exert additive and/or synergistic effects to provide enhanced health benefits on a variety of physiological and biochemical levels including hormone metabolism, immune system functioning, and gene expression profiles. Plant and vegetable extracts have been shown to possess anti-hyperglycemic properties in animal models of diabetes, such as in mulberry (Andallu and Varadacharyulu 2003, Clin. Chim. Acta, 338, 3-10), Aegle marmelos (Kamalakkannan and Prince, 2003, J. Ethnopharmacol., 87, 207-210), and chard (Bolkent et al., 2000, J. Ethnopharmacol., 73, 251-259).
Potatoes are an excellent source of phenolic compounds Camire et al 2009, Crit. Rev. Food Sci. Nutr., 49, 823-840) that have been linked with glucose-lowering effects in animal feeding trials using potato peel powder (Singh et al., 2005, Plant Foods Hum. Nutr. 60, 49-54). Mild suppression of body weight gain and inhibition of abdominal fat accumulation had been noted in high fat-fed rats supplemented with anthocyanin-rich purple fleshed potato ethanolic extracts (Yoon et al., 2008, J. Ethnopharmacol., 118, 396-404). Feeding pure chlorogenic acid or ferulic acid has been reported to have anti-obesity and hypoglycemic activity in animals (Cho et al., Food Chem. Toxicol. (2010) 48, 937-943; Jin Son et al., J. Clin. Biochem. Nutr. (2010) 46, 150-156, Tunnicliffe, et al., Appl. Physiol. Nutr. Metab. (2011) 36, 650-659; Ohnishi et al.; Biofactors (2004) 21, 315-319. and Shimoda et al., Altern. Med. 2006, 6, 9.
Despite these advances, researchers continue to pursue new ways of deriving health benefits from naturally occurring antioxidants, and to investigate the minimally essential components for a nutraceutical composition to reproducibly show health effects in obesity and type 2 diabetes.